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16 - Proteins and symptoms

from Section 2 - Cancer Symptom Mechanisms and Models: Clinical and Basic Science

Published online by Cambridge University Press:  05 August 2011

By
Bang-Ning Lee  and
James M. Reuben
Edited by
Charles S. Cleeland ,
Michael J. Fisch  and
Adrian J. Dunn
Bang-Ning Lee
Affiliation:
The University of Texas M. D. Anderson Cancer Center
James M. Reuben
Affiliation:
The University of Texas M. D. Anderson Cancer Center
Charles S. Cleeland
Affiliation:
University of Texas, M. D. Anderson Cancer Center
Michael J. Fisch
Affiliation:
University of Texas, M. D. Anderson Cancer Center
Adrian J. Dunn
Affiliation:
University of Hawaii, Manoa
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Summary

Multiple and severe symptoms profoundly affect the quality of life of cancer patients and their families, and also are a significant challenge for those who manage patients with cancer. Untreated symptoms can negatively influence the effectiveness of curative treatment by interrupting or terminating therapy. It is likely that the association of co-occurring symptoms reflects a common underlying mechanism.

Some self-reported symptoms have been related to the actions of specific cytokines that appear to produce a constellation of symptoms and behavioral signs when given exogenously to both humans and animals. The notion that proinflammatory cytokines play a pivotal role in the pathophysiology of cancer-related symptoms comes from several convergent lines of experimental and clinical research that are not limited to the study of cancer. Inflammation is now recognized as a critical component of tumor progression because many cancers arise from sites of infection, chronic irritation, and inflammation, and tumor cells co-opt some of the signaling molecules of the innate immune system for invasion, migration, and metastasis.

This chapter considers the role of inflammation in the production of symptoms in cancer and other chronic diseases and examines emerging therapeutic approaches for treating cancer and its symptoms.

Type
Chapter
Information
Cancer Symptom Science
Measurement, Mechanisms, and Management
 , pp. 179 - 191
Publisher: Cambridge University Press
Print publication year: 2010

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References

Lee, BN, Dantzer, R, Langley, KE, et al. A cytokine-based neuroimmunologic mechanism of cancer-related symptoms. Neuroimmunomodulation 11(5):279–292, 2004.CrossRefGoogle ScholarPubMed
Coussens, LM, Werb, Z. Inflammation and cancer. Nature 420(6917):860–867, 2002.CrossRefGoogle ScholarPubMed
Rivest, S, Lacroix, S, Vallières, L, Nadeau, S, Zhang, J, Laflamme, N. How the blood talks to the brain parenchyma and the paraventricular nucleus of the hypothalamus during systemic inflammatory and infectious stimuli. Proc Soc Exp Biol Med 223(1):22–38, 2000.CrossRefGoogle ScholarPubMed
Craig, R, Larkin, A, Mingo, AM, et al. p38 MAPK and NF-kappa B collaborate to induce interleukin-6 gene expression and release: evidence for a cytoprotective autocrine signaling pathway in a cardiac myocyte model system. J Biol Chem 275(31):23814–23824, 2000.CrossRefGoogle Scholar
Hierholzer, C, Kalff, JC, Bednarski, B, et al. Rapid and simultaneous activation of Stat3 and production of interleukin 6 in resuscitated hemorrhagic shock. Arch Orthop Trauma Surg 119:332–336, 1999.CrossRefGoogle ScholarPubMed
,Oncology Nursing Society. Welcome to CancerSymptoms.org. Available from: URL: www.cancersymptoms.org. Accessed Oct 29, 2008.
Cleeland, CS. Cancer-related symptoms. Semin Radiat Oncol 10(3):175–190, 2000.CrossRefGoogle ScholarPubMed
Patrick, DL, Ferketich, SL, Frame, PS, et al. National Institutes of Health State-of-the-Science Conference Statement: Symptom Management in Cancer: Pain, Depression, and Fatigue, July 15–17, 2002. J Natl Cancer Inst Monogr 32:9–16, 2004.Google Scholar
Meyers, CA, Abbruzzese, JL. Cognitive functioning in cancer patients: effect of previous treatment. Neurology 42:434–436, 1992.CrossRefGoogle ScholarPubMed
Meyers, CA, Valentine, AD. Neurological and psychiatric adverse effects of immunological therapy. CNS Drugs 3:56–68, 1995.CrossRefGoogle Scholar
Valentine, AD, Meyers, CA. Neurobehavioral effects of interferon therapy. Curr Psychiatry Rep 7:391–395, 2005.CrossRefGoogle ScholarPubMed
Vojdani, A, Lapp, CW. Interferon-induced proteins are elevated in blood samples of patients with chemically or virally induced chronic fatigue syndrome. Immunopharmacol Immunotoxicol 21:175–202, 1999.CrossRefGoogle ScholarPubMed
Kurzrock, R. The role of cytokines in cancer-related fatigue. Cancer 92(6 Suppl):1684–1688, 2001.3.0.CO;2-Z>CrossRefGoogle ScholarPubMed
Bower, JE, Ganz, PA, Aziz, N, Fahey, JL. Fatigue and proinflammatory cytokine activity in breast cancer survivors. Psychosom Med 64(4):604–611, 2002.CrossRefGoogle ScholarPubMed
Wang, XS, Giralt, SA, Mendoza, TR, et al. Clinical factors associated with cancer-related fatigue in patients being treated for leukemia and non-Hodgkin's lymphoma. J Clin Oncol 20:1319–1328, 2002.Google ScholarPubMed
Mantovani, G, Macciò, A, Lai, P, Massa, E, Ghiani, M, Santona, MC. Cytokine involvement in cancer anorexia/cachexia: role of megestrol acetate and medroxyprogesterone acetate on cytokine downregulation and improvement of clinical symptoms. Crit Rev Oncog 9:99–106, 1998.CrossRefGoogle ScholarPubMed
Rowinsky, EK, Chaudhry, V, Forastiere, AA, et al. Phase I and pharmacologic study of paclitaxel and cisplatin with granulocyte colony-stimulating factor: neuromuscular toxicity is dose-limiting. J Clin Oncol 11:2010–2020, 1993.CrossRefGoogle ScholarPubMed
Weintraub, M, Adde, MA, Venzon, DJ, et al. Severe atypical neuropathy associated with administration of hematopoietic colony-stimulating factors and vincristine. J Clin Oncol 14:935–940, 1996.CrossRefGoogle ScholarPubMed
Basu, S, Sodhi, A. Increased release of interleukin-1 and tumor necrosis factor by interleukin-2-induced lymphokine-activated killer cells in the presence of cisplatin and FK-565. Immunol Cell Biol 70:15–24, 1992.CrossRefGoogle ScholarPubMed
Gan, XH, Jewett, A, Bonavida, B. Activation of human peripheral blood-derived monocytes by cis-diamminedichloroplatinum: enhanced tumoricidal activity and secretion of tumor necrosis factor-alpha. Nat Immun 11:144–155, 1992.Google ScholarPubMed
O'Brien, JM, Wewers, MD, Moore, SA, Allen, JN. Taxol and colchicine increase LPS-induced pro-IL-1 beta production, but do not increase IL-1 beta secretion: a role for microtubules in the regulation of IL-1 beta production. J Immunol 154(8):4113–4122, 1995.Google Scholar
Zaks-Zilberman, M, Zaks, TZ, Vogel, SN. Induction of proinflammatory and chemokine genes by lipopolysaccharide and paclitaxel (Taxol) in murine and human breast cancer cell lines. Cytokine 15(3):156–165, 2001.CrossRefGoogle ScholarPubMed
Ogura, K, Ohta, S, Ohmori, T, et al. Vinca alkaloids induce granulocyte-macrophage colony stimulating factor in human peripheral blood mononuclear cells. Anticancer Res 20:2383–2388, 2000.Google ScholarPubMed
Dougherty, PM, Palecek, J, Palecková, V, Sorkin, LS, Willis, WD. The role of NMDA and non-NMDA excitatory amino acid receptors in the excitation of primate spinothalamic tract neurons by mechanical, thermal, chemical, and electrical stimuli. J Neurosci 12:3025–3041, 1992.CrossRefGoogle ScholarPubMed
Lee, BN, Andersson, B, Cohen, MZ, et al. Relationship between plasma cytokine levels and self-reported symptoms in AML patients pre- and post-transplantation with allogeneic peripheral blood stem cells [abstract]. American Society of Hematology 45th Annual Meeting and Exposition, San Diego CA, December 6–9, 2003. Blood 102(11):966A, 2003. Abstract 3600.Google Scholar
Zlotnik, A. Chemokines and cancer. Int J Cancer 119:2026–2029, 2006.CrossRefGoogle ScholarPubMed
Laverdiere, C, Gorlick, R. CXCR4 expression in osteosarcoma cell lines and tumor samples: evidence for expression by tumor cells. Clin Cancer Res 12(17):5254, 2006.CrossRefGoogle Scholar
Wang, J, Xi, L, Gooding, W, Godfrey, TE, Ferris, RL. Chemokine receptors 6 and 7 identify a metastatic expression pattern in squamous cell carcinoma of the head and neck. Adv Otorhinolaryngol 62:121–133, 2005.Google ScholarPubMed
Diaz, GA. CXCR4 mutations in WHIM syndrome: a misguided immune system?Immunol Rev 203:235–243, 2005.CrossRefGoogle ScholarPubMed
Feldmann, M. What is the mechanism of action of anti-tumour necrosis factor-alpha antibody in rheumatoid arthritis?Int Arch Allergy Immunol 111:362–365, 1996.CrossRefGoogle ScholarPubMed
Ardizzone, S, Bianchi Porro, G. Biologic therapy for inflammatory bowel disease. Drugs 65:2253–2286, 2005.CrossRefGoogle ScholarPubMed
Karin, M, Cao, Y, Greten, FR, Li, ZW. NF-kB in cancer: from innocent bystander to major culprit. Nature Rev Cancer 2(4):301–310, 2002.CrossRefGoogle ScholarPubMed
Karin, M. Nuclear factor-kappaB in cancer development and progression. Nature 441:431–436, 2006.CrossRefGoogle ScholarPubMed
Yamamoto, Y, Gaynor, RB. Therapeutic potential of inhibition of the NF-kB pathway in the treatment of inflammation and cancer. J Clin Invest 107(2):134–142, 2001.CrossRefGoogle ScholarPubMed
Surh, YJ, Chun, KS, Cha, HH, et al. Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-kappa B activation. Mutation Res 480–481:243–268, 2001.CrossRefGoogle ScholarPubMed
Rivest, S. What is the cellular source of prostaglandins in the brain in response to systemic inflammation? Facts and controversies. Molec Psychiatry 4:500–507, 1999.CrossRefGoogle ScholarPubMed
O'Shea, JJ, Murray, PJ. Cytokine signaling modules in inflammatory responses. Immunity 28(4):477–487, 2008.CrossRefGoogle ScholarPubMed
Lotz, M, Vaughan, JH, Carson, DA. Effect of neuropeptides on production of inflammatory cytokines by human monocytes. Science 241:1218–1221, 1988.CrossRefGoogle ScholarPubMed
Elenkov, IJ, Wilder, RL, Chrousos, GP, Vizi, ES. The sympathetic nerve – an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev 52:595–638, 2000.Google ScholarPubMed
Elenkov, IJ, Webster, E, Papanicolaou, DA, Fleisher, TA, Chrousos, GP, Wilder, RL. Histamine potently suppresses human IL-12 and stimulates IL-10 production via H2 receptors. J Immunol 161:2586–2593, 1998.Google ScholarPubMed
Trikha, M, Corringham, R, Klein, B, Rossi, JF. Targeted anti-interleukin-6 monoclonal antibody therapy for cancer: a review of the rationale and clinical evidence. Clin Cancer Res 9:4653–4665, 2003.Google ScholarPubMed
Tilg, H, Trehu, E, Atkins, MB, Dinarello, CA, Mier, JW. Interleukin-6 (IL-6) as an anti-inflammatory cytokine: induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55. Blood 83(1):113–118, 1994.Google ScholarPubMed
Schindler, R, Mancilla, J, Endres, S, Ghorbani, R, Clark, SC, Dinarello, CA. Correlations and interactions in the production of interleukin-6 (IL- 6), IL-1, and tumor necrosis factor (TNF) in human blood mononuclear cells: IL-6 suppresses IL-1 and TNF. Blood 75(1):40–47, 1990.Google ScholarPubMed
Korth, C, Mullington, J, Schreiber, W, Pollmächer, T. Influence of endotoxin on daytime sleep in humans. Infect Immun 64:1110–1115, 1996.Google ScholarPubMed
Born, J, Späth-Schwalbe, E, Schwakenhofer, H, Kern, W, Fehm, HL. Influences of corticotropin-releasing hormone, adrenocorticotropin, and cortisol on sleep in normal man. J Clin Endocrinol Metab 68(5):904–911, 1989.CrossRefGoogle ScholarPubMed
Cidlowski, JA, Bellingham, DL, Powell-Oliver, FE, Lubahn, DB, Sar, M. Novel antipeptide antibodies to the human glucocorticoid receptor: recognition of multiple receptor forms in vitro and distinct localization of cytoplasmic and nuclear receptors. Mol Endocrinol 4:1427–1437, 1990.CrossRefGoogle ScholarPubMed
Auphan, N, DiDonato, JA, Rosette, C, Helmberg, A, Karin, M. Immunosuppression by glucocorticoids: inhibition of NF-kappaB activity through induction of I kappa B synthesis. Science 270:286–290, 1995.CrossRefGoogle ScholarPubMed
Ramdas, J, Harmon, J. Glucocorticoid-induced apoptosis and regulation of NF-kappaB activity in human leukemic T cells. Endocrinology 139:3813–3821, 1998.CrossRefGoogle ScholarPubMed
Scheinman, R, Cogswell, P, Lofquist, A, Baldwin, A. Role of transcriptional activation of I kappaB in mediation of immunosuppression by glucocorticoids. Science 270:283–286, 1995.CrossRefGoogle ScholarPubMed
Karayiannakis, AJ, Syrigos, KN, Polychronidis, A, Pitiakoudis, M, Bounovas, A, Simopoulos, K. Serum levels of tumor necrosis factor-alpha and nutritional status in pancreatic cancer patients. Anticancer Res 21:1355–1358, 2001.Google ScholarPubMed
Yoshida, N, Ikemoto, S, Narita, K, et al. Interleukin-6, tumour necrosis factor alpha and interleukin-1beta in patients with renal cell carcinoma. Br J Cancer 86:1396–1400, 2002.CrossRefGoogle ScholarPubMed
Bozcuk, H, Uslu, G, Samur, M, et al. Tumour necrosis factor-alpha, interleukin-6, and fasting serum insulin correlate with clinical outcome in metastatic breast cancer patients treated with chemotherapy. Cytokine 27:58–65, 2004.CrossRefGoogle ScholarPubMed
Michalaki, V, Syrigos, KN, Charles, P, Waxman, J. Serum levels of IL-6 and TNF-alpha correlate with clinicopathological features and patient survival in patients with prostate cancer. Br J Cancer 90:2312–2316, 2004.CrossRefGoogle ScholarPubMed
List, A, Kurtin, S, Roe, DJ, et al. Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med 352(6):549–557, 2005.CrossRefGoogle ScholarPubMed
Richardson, PG, Blood, E, Mitsiades, CS, et al. A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma. Blood 108(10):3458–3464, 2006.CrossRefGoogle ScholarPubMed
Ferrajoli, A, Lee, BN, Schlette, EJ, et al. Lenalidomide induces complete and partial remissions in patients with relapsed and refractory chronic lymphocytic leukemia. Blood 111(11):5291–5297, 2008.CrossRefGoogle ScholarPubMed
Field-Smith, A, Morgan, GJ, Davies, FE. Bortezomib (Velcade®) in the treatment of multiple myeloma. Ther Clin Risk Manag 2(3):271–279, 2006.CrossRefGoogle Scholar
Dominguez, C, Powers, DA, Tamayo, N. p38 MAP kinase inhibitors: many are made, but few are chosen. Curr Opin Drug Discov Devel 8(4):421–430, 2005.Google ScholarPubMed
Voorhees, PM, Chen, Q, Kuhn, DJ, et al. Inhibition of interleukin-6 signaling with CNTO 328 enhances the activity of bortezomib in preclinical models of multiple myeloma. Clin Cancer Res 13(21):6469–6478, 2007.CrossRefGoogle ScholarPubMed
Paul-Pletzer, K. Tocilizumab: blockade of interleukin-6 signaling pathway as a therapeutic strategy for inflammatory disorders. Drugs Today (Barc) 42:559–576, 2006.CrossRefGoogle ScholarPubMed
Nishimoto, N. Clinical studies in patients with Castleman's disease, Crohn's disease, and rheumatoid arthritis in Japan. Clin Rev Allergy Immunol 28:221–230, 2005.CrossRefGoogle ScholarPubMed
Baggiolini, M, Dewald, B, Moser, B. Interleukin-8 and related chemotactic cytokines – CXC and CC chemokines. Adv Immunol 55:97–179, 1994.CrossRefGoogle ScholarPubMed
Singh, RK, Varney, ML, Bucana, CD, Johansson, SL. Expression of interleukin-8 in primary and metastatic malignant melanoma of the skin. Melanoma Res 9:383–387, 1999.CrossRefGoogle ScholarPubMed
Masuya, D, Huang, CL, Liu, D, et al. The intratumoral expression of vascular endothelial growth factor and interleukin-8 associated with angiogenesis in nonsmall cell lung carcinoma patients. Cancer 92(10):2628–2638, 2001.3.0.CO;2-F>CrossRefGoogle ScholarPubMed
Eisma, RJ, Spiro, JD, Kreutzer, DL. Role of angiogenic factors: coexpression of interleukin-8 and vascular endothelial growth factor in patients with head and neck squamous carcinoma. Laryngoscope 109(5):687–693, 1999.CrossRefGoogle ScholarPubMed
Huang, S, Mills, L, Mian, B, et al. Fully humanized neutralizing antibodies to interleukin-8 (ABX-IL8) inhibit angiogenesis, tumor growth, and metastasis of human melanoma. Am J Pathol 161:125–134, 2002.CrossRefGoogle ScholarPubMed
Yang, XD, Corvalan, JR, Wang, P, Roy, CM, Davis, CG. Fully human anti-interleukin-8 monoclonal antibodies: potential therapeutics for the treatment of inflammatory disease states. J Leukoc Biol 66:401–410, 1999.CrossRefGoogle ScholarPubMed
Melnikova, VO, Bar-Eli, M. Bioimmunotherapy for melanoma using fully human antibodies targeting MCAM/MUC18 and IL-8. Pigment Cell Res 19:395–405, 2006.CrossRefGoogle ScholarPubMed
Harvey, JR, Mellor, P, Eldaly, H, Lennard, TW, Kirby, JA, Ali, S. Inhibition of CXCR4-mediated breast cancer metastasis: a potential role for heparinoids?Clin Cancer Res 13:1562–1570, 2007.CrossRefGoogle ScholarPubMed
Tamamura, H, Hori, A, Kanzaki, N. T140 analogs as CXCR4 antagonists identified as anti-metastatic agents in the treatment of breast cancer. FEBS Lett 550:79–83, 2003.CrossRefGoogle ScholarPubMed
Takenaga, M, Tamamura, H, Hiramatsu, K. A single treatment with microcapsules containing a CXCR4 antagonist suppresses pulmonary metastasis of murine melanoma. Biochem Biophys Res Commun 320:226–232, 2004.CrossRefGoogle ScholarPubMed
Liang, Z, Yoon, Y, Votaw, J, Goodman, MM, Williams, L, Shim, H. Silencing of CXCR4 blocks breast cancer metastasis. Cancer Res 65:967–971, 2005.Google ScholarPubMed
Kim, SY, Lee, CH, Midura, BV, et al. Inhibition of the CXCR4/CXCL12 chemokine pathway reduces the development of murine pulmonary metastases. Clin Exp Metastasis 25(3):201–211, 2008.CrossRefGoogle ScholarPubMed
Devine, SM, Flomenberg, N, Vesole, DH, et al. Rapid mobilization of CD34+ cells following administration of the CXCR4 antagonist AMD3100 to patients with multiple myeloma and non-Hodgkin's lymphoma. J Clin Oncol 22:1095–1102, 2004.CrossRefGoogle ScholarPubMed
Siwak, DR, Shishodia, S, Aggarwal, BB, Kurzrock, R. Curcumin-induced antiproliferative and proapoptotic effects in melanoma cells are associated with suppression of Ikappa B kinase and nuclear factor kappaB activity and are independent of the B-Raf/mitogen-activated/extracellular signal-regulated protein kinase pathway and the Akt pathway. Cancer 104(4):879–890, 2005.CrossRefGoogle Scholar
Hanai, H, Iida, T, Takeuchi, K, et al. Curcumin maintenance therapy for ulcerative colitis: randomized, multicenter, double-blind, placebo-controlled trial. Clin Gastroenterol Hepatol 4(12):1502–1506, 2006.CrossRefGoogle ScholarPubMed
Holt, PR, Katz, S, Kirshoff, R. Curcumin therapy in inflammatory bowel disease: a pilot study. Dig Dis Sci 50:2191–2193, 2005.CrossRefGoogle ScholarPubMed

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